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PGLYRP2 drives hepatocyte-intrinsic innate immunity by trapping and clearing hepatitis B virus. J. Clin. Invest. (IF 13.3) Pub Date : 2025-02-13 Ying Li,Huihui Ma,Yongjian Zhang,Tinghui He,Binyang Li,Haoran Ren,Jia Feng,Jie Sheng,Kai Li,Yu Qian,Yunfeng Wang,Haoran Zhao,Jie He,Huicheng Li,Hongjin Wu,Yuanfei Yao,Ming Shi
Spontaneous clearance of hepatitis B virus (HBV) is frequent in adults (95%) but rare in infants (5%), emphasizing the critical role of age-related hepatic immunocompetence. However, the underlying mechanisms of hepatocyte-specific immunosurveillance and age-dependent HBV clearance remain unclear. Here, we identified PGLYRP2 as a hepatocyte-specific pattern recognition receptor with age-dependent expression
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Metastatic Tumor Growth in Steatotic Liver is Promoted by HAS2-Mediated Fibrotic Tumor Microenvironment. J. Clin. Invest. (IF 13.3) Pub Date : 2025-02-13 Yoon Mee Yang,Jieun Kim,Zhijun Wang,Jina Kim,So Yeon Kim,Gyu Jeong Cho,Jee Hyung Lee,Sun Myoung Kim,Takashi Tsuchiya,Michitaka Matsuda,Vijay Pandyarajan,Stephen J Pandol,Michael S Lewis,Alexandra Gangi,Paul W Noble,Dianhua Jiang,Akil Merchant,Edwin M Posadas,Neil A Bhowmick,Shelly C Lu,Sungyong You,Alexander M Xu,Ekihiro Seki
Steatotic liver enhances liver metastasis of colorectal cancer, but this process is not fully understood. Steatotic liver induced by a high-fat diet (HFD) increases cancer-associated fibroblast (CAF) infiltration and collagen and hyaluronic acid (HA) production. We investigated the role of HA synthase 2 (HAS2) in the fibrotic tumor microenvironment in steatotic liver using Has2ΔHSC mice, in which Has2
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XN-1000 Hematology Analyzer as an Alternative to Flow Cytometry for Measuring Residual Cells in Blood Components. Ann. Lab. Med. (IF 4.0) Pub Date : 2025-02-12 Anita Siller,Lisa Seekircher,Daniela Schmidt,Lena Tschiderer,Peter Willeit,Harald Schennach,Marco Amato
Background Measuring residual cells in blood products is legally required for monitoring the manufacturing process and ensuring recipient safety. We compared the accuracy and performance of the two methodologies. Methods Residual white blood cells (rWBCs), red blood cells (rRBCs), and platelets (rPLTs) were measured in RBC concentrates (rWBCs), fresh frozen plasma (rWBCs, rRBCs, and rPLTs), and PLT
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Complement Activation and Hemolysis in Non-Human Primates Following Transfusion of Genetically Modified Pig Red Blood Cells. Ann. Lab. Med. (IF 4.0) Pub Date : 2025-02-12 Hee Jung Kang,Juhye Roh,Haneulnari Lee,Eun Mi Park,Hye Won Lee,Ju Young Lee,Jeong Ho Hwang,Joohyun Shim,Kimyung Choi
Background Pig red blood cells (RBCs) are rapidly eliminated when transfused into nonhuman primates (NHPs) because of immune reactions involving antibody binding and complement activation. We assessed the relationship between post-transfusion hemolysis and complement activation. Methods RBCs for transfusion were prepared from wild-type (WT) and genetically modified pigs and NHPs. After the withdrawal
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Safety and efficacy of pharmacological inhibition of ketohexokinase in hereditary fructose intolerance. J. Clin. Invest. (IF 13.3) Pub Date : 2025-02-11 Evi Jc Koene,Amée M Buziau,David Cassiman,Timothy M Cox,Judith Bons,Jean L J M Scheijen,Casper G Schalkwijk,Steven Jr Meex,Aditi R Saxena,William P Esler,Vera B Schrauwen-Hinderling,Patrick Schrauwen,Martijn Cgj Brouwers
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TRAF3 loss protects glioblastoma cells from lipid peroxidation and immune elimination via dysregulated lipid metabolism. J. Clin. Invest. (IF 13.3) Pub Date : 2025-02-11 Yu Zeng,Liqian Zhao,Kunlin Zeng,Ziling Zhan,Zhengming Zhan,Shangbiao Li,Hongchao Zhan,Peng Chai,Cheng Xie,Shengfeng Ding,Yuxin Xie,Li Wang,Cuiying Li,Xiaoxia Chen,Daogang Guan,Enguang Bi,Jian-You Liao,Fan Deng,Xiaochun Bai,Ye Song,Aidong Zhou
Glioblastoma (GBM) is a highly aggressive form of brain tumor characterized by dysregulated metabolism. Increased fatty acid oxidation (FAO) protects tumor cells from lipid peroxidation-induced cell death, although the precise mechanisms involved remain unclear. Herein, we report that loss of tumor necrosis factor receptor-associated factor 3 (TRAF3) in GBM critically regulates lipid peroxidation and
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TRIB3 mediates vascular calcification through facilitating self-ubiquitination and dissociation of Smurf1 in chronic renal disease. J. Clin. Invest. (IF 13.3) Pub Date : 2025-02-11 Yihui Li,Chang Ma,Yanan Sheng,Shanying Huang,Huaibing Sun,Yun Ti,Zhihao Wang,Feng Wang,Fangfang Chen,Chen Li,Haipeng Guo,Mengxiong Tang,Fangqiang Song,Hao Wang,Ming Zhong
The osteogenic environment promotes vascular calcium phosphate deposition and aggregation of unfolded and misfolded proteins, resulting in endoplasmic reticulum (ER) stress in chronic renal disease (CKD). Controlling ER stress through genetic intervention is a promising approach for treating vascular calcification. In this study, we demonstrated a positive correlation between ER stress-induced tribble
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Ablating VHL in Rod Photoreceptors Modulates RPE Glycolysis and Improves Preclinical Model of Retinitis Pigmentosa. J. Clin. Invest. (IF 13.3) Pub Date : 2025-02-11 Salvatore Marco Caruso,Xuan Cui,Brian M Robbings,Noah Heaps,Aykut Demikrol,Bruna Lopes da Costa,Daniel T Hass,Peter Mj Quinn,Jianhai Du,James B Hurley,Stephen H Tsang
Neuroretinal degenerations including retinitis pigmentosa (RP) comprise a heterogeneous collection of pathogenic mutations that ultimately result in blindness. Despite recent advances in precision medicine, therapies for rarer mutations are hindered by burdensome developmental costs. To this end, Von Hippel-Lindau (VHL) is an attractive therapeutic target to treat RP. By ablating VHL in rod photoreceptors
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MBNL overexpression rescues cardiac phenotypes in a myotonic dystrophy type 1 heart mouse model. J. Clin. Invest. (IF 13.3) Pub Date : 2025-02-11 Rong-Chi Hu,Yi Zhang,Larissa Nitschke,Sara J Johnson,Ayrea E Hurley,William R Lagor,Zheng Xia,Thomas A Cooper
Myotonic Dystrophy Type 1 (DM1) is an autosomal dominant disease caused by a CTG repeat expansion in the DMPK gene. The expanded CUG repeat RNA (CUGexp RNA) transcribed from the mutant allele sequesters the muscleblind-like (MBNL) family of RNA-binding proteins, causing their loss of function and disrupting regulated pre-mRNA processing. We used a DM1 heart mouse model that inducibly expresses CUGexp
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Endothelial-specific postnatal deletion of Nos3 preserves intraocular pressure homeostasis via macrophage recruitment and NOS2 upregulation. J. Clin. Invest. (IF 13.3) Pub Date : 2025-02-11 Ruth A Kelly,Megan S Kuhn,Ester Reina-Torres,Revathi Balasubramanian,Kristin M Perkumas,Guorong Li,Takamune Takahashi,Simon Wm John,Michael H Elliott,Darryl R Overby,W Daniel Stamer
Polymorphisms in Nos3 increases risk for glaucoma, the leading cause of irreversible blindness worldwide. A key modifiable risk factor for glaucoma is intraocular pressure (IOP), which is regulated by nitric oxide (NO), a product of nitric oxide synthase-3 (Nos3) in Schlemm's canal of the conventional outflow pathway. We studied the effects of a conditional, endothelial-specific postnatal deletion
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Laboratory Monitoring in Transgender and Gender-Diverse Individuals. Clin. Chem. (IF 7.1) Pub Date : 2025-02-10 Brendan J Nolan,Ada S Cheung
BACKGROUND Increasing numbers of transgender and gender-diverse individuals are seeking initiation of gender-affirming hormone therapy. This aligns an individual's physical characteristics with their gender identity and improves psychological outcomes. Physical changes, including changes to muscle mass and body fat redistribution, can alter sex-specific laboratory reference ranges. CONTENT We review
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Improved 1H Nuclear Magnetic Resonance Spectroscopy Quantification of Plasma Creatinine. Clin. Chem. (IF 7.1) Pub Date : 2025-02-10 Karen Friederike Gauß,Nele Friedrich,Ann-Kristin Henning,Marc Fenzlaff,Stephanie Könemann,Daniel Rosenkranz,Astrid Petersmann,Matthias Nauck
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The Slow Progress in Developing Better Long-Term Cardiovascular Risk Assessment in Women Continues. Clin. Chem. (IF 7.1) Pub Date : 2025-02-10 Leslie J Donato,Kyla M Lara-Breitinger,Allan S Jaffe
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Cardiac Biomarkers and Malnutrition Incidence in Community-Dwelling Older Adults without Cardiovascular Disease: The Seniors-ENRICA-2 Cohort. Clin. Chem. (IF 7.1) Pub Date : 2025-02-07 Blanca Fabre-Estremera,Antonio Buño-Soto,Mercedes Sotos-Prieto,Adrián Carballo-Casla,Samara Palma Milla,Fernando Rodríguez-Artalejo,Rosario Ortolá
BACKGROUND Given the close relationship between cardiovascular disease (CVD) and malnutrition, we examined whether higher concentrations of high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP), which indicate CVD risk in the general population, were prospectively associated with malnutrition incidence in community-dwelling older adults without CVD.
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Beclin 1 prevents ISG15-mediated cytokine storms to secure fetal hematopoiesis and survival J. Clin. Invest. (IF 13.3) Pub Date : 2024 Wen Wei, Xueqin Gao, Jiawei Qian, Lei Li, Chen Zhao, Li Xu, Yanfei Zhu, Zhenzhen Liu, Nengrong Liu, Xueqing Wang, Zhicong Jin, Bowen Liu, Lan Xu, Jin Dong, Suping Zhang, Jiarong Wang, Yumu Zhang, Yao Yu, Zhanjun Yan, Yanjun Yang, Jie Lu, Yixuan Fang, Na Yuan, Jianrong Wang
Proper control of inflammatory responses is essential for embryonic development, but the underlying mechanism is poorly understood. Here, we show that under physiological conditions, inactivation of ISG15, an inflammation amplifier, is associated with the interaction of Beclin 1 (Becn1), via its evolutionarily conserved domain, with STAT3 in the major fetal hematopoietic organ of mice. Conditional
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Metalloproteinase inhibitors regulate biliary progenitor cells through sDLK1 in organoid models of liver injury J. Clin. Invest. (IF 13.3) Pub Date : 2024 Virginie Defamie, Kazeera Aliar, Soumili Sarkar, Foram Vyas, Ronak Shetty, Swami Reddy Narala, Hui Fang, Sanjay Saw, Pirashaanthy Tharmapalan, Otto Sanchez, Jennifer J. Knox, Paul D. Waterhouse, Rama Khokha
Understanding cell fate regulation in the liver is necessary to advance cell therapies for hepatic disease. Liver progenitor cells (LPCs) contribute to tissue regeneration after severe hepatic injury, yet signals instructing progenitor cell dynamics and fate are largely unknown. Tissue inhibitor of metalloproteinases 1 (TIMP1) and TIMP3 control the sheddases ADAM10 and ADAM17, key for NOTCH activation
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Fusobacterium nucleatum promotes colorectal cancer through neogenesis of tumor stem cells J. Clin. Invest. (IF 13.3) Pub Date : 2024 Qinying Wang, Tingting Hu, Qinyuan Zhang, Yichi Zhang, Xiaoxu Dong, Yutao Jin, Jinming Li, Yangyang Guo, Fanying Guo, Ziying Chen, Peijie Zhong, Yongzhi Yang, Yanlei Ma
Intestinal stem cells are crucial for maintaining intestinal homeostasis, yet their transformation into tumor stem cells in the context of microbial infection remains poorly understood. Fusobacterium nucleatum is frequently associated with the onset and progression of colorectal cancer (CRC). In this study, we uncovered that F. nucleatum colonized the depths of gut crypts in both patients with CRC
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A deafness-blindness syndrome results from ATF6-based disruption of the unfolded protein response J. Clin. Invest. (IF 13.3) Pub Date : 2025 Yuvraj Joshi, Jeffrey N. Savas
Sensorineural hearing loss (SNHL) is the most prevalent form of permanent hearing impairment, arising from factors such as aging, exposure to loud noise, disease, ototoxic medications, and genetic mutations. Despite extensive research, effective treatments or cures for SNHL remain elusive. In this issue of the JCI, Lee et al. reveal a link between mutations in ATF6 and SNHL in patients with achromatopsia
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Mutations in unfolded protein response regulator ATF6 cause hearing and vision loss syndrome J. Clin. Invest. (IF 13.3) Pub Date : 2024 Eun-Jin Lee, Kyle Kim, Monica Sophia Diaz-Aguilar, Hyejung Min, Eduardo Chavez, Korina J. Steinbergs, Lance A. Safarta, Guirong Zhang, Allen F. Ryan, Jonathan H. Lin
Activating transcription factor 6 (ATF6) is a key regulator of the unfolded protein response (UPR) and is important for ER function and protein homeostasis in metazoan cells. Patients carrying loss-of-function ATF6 disease alleles develop the cone dysfunction disorder achromatopsia. The effect of loss of ATF6 function on other cell types, organs, and diseases in people remains unclear. Here, we report
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NEDD4L mediates intestinal epithelial cell ferroptosis to restrict inflammatory bowel diseases and colorectal tumorigenesis J. Clin. Invest. (IF 13.3) Pub Date : 2024 Jingjing Liang, Ning Wang, Yihan Yao, Yingmei Wang, Xiang An, Haofei Wang, Huan Liu, Yu Jiang, Hui Li, Xiaoqing Cheng, Jiaqi Xu, Xiaojing Liang, Jun Lou, Zengfeng Xin, Ting Zhang, Xiaojian Wang, Wenlong Lin
Various factors play key roles in maintaining intestine homeostasis. Disruption of the balance may lead to inflammatory bowel diseases and even colorectal cancer (CRC). Loss or gain of function of many key proteins can result in dysregulated intestinal homeostasis. Our research demonstrated that neural precursor cells expressed developmentally downregulated 4–like protein (NEDD4L, or NEDD4-2), a type
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Gene-replacement therapy in neurodevelopmental disorders: progress and challenges J. Clin. Invest. (IF 13.3) Pub Date : 2025 Holger Lerche, Ulrike B.S. Hedrich, Thomas V. Wuttke
Heterozygous loss-of-function variants in the SLC6A1 gene, encoding GAT1, which is the main GABA transporter in the brain, lead to a broad spectrum of neuropsychiatric and neurodevelopmental disorders including epilepsy, developmental delay, intellectual disability, and autism. Gene-replacement strategies involving adeno-associated viruses (AAV) require the delivery of genes to specific types of neurons
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The gut microbiome and cancer response to immune checkpoint inhibitors J. Clin. Invest. (IF 13.3) Pub Date : 2025 Francesca S. Gazzaniga, Dennis L. Kasper
Immune checkpoint inhibitors (ICIs) are widely used for cancer immunotherapy, yet only a fraction of patients respond. Remarkably, gut bacteria impact the efficacy of ICIs in fighting tumors outside of the gut. Certain strains of commensal gut bacteria promote antitumor responses to ICIs in a variety of preclinical mouse tumor models. Patients with cancer who respond to ICIs have a different microbiome
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Structural characterization of human monoclonal antibodies targeting uncommon antigenic sites on spike glycoprotein of SARS-CoV J. Clin. Invest. (IF 13.3) Pub Date : 2024 Naveenchandra Suryadevara, Nurgun Kose, Sandhya Bangaru, Elad Binshtein, Jennifer Munt, David R. Martinez, Alexandra Schäfer, Luke Myers, Trevor D. Scobey, Robert H. Carnahan, Andrew B. Ward, Ralph S. Baric, James E. Crowe Jr
The function of the spike protein N terminal domain (NTD) in coronavirus (CoV) infections is poorly understood. However, some rare antibodies that target the SARS-CoV-2 NTD potently neutralize the virus. This finding suggests the NTD may contribute, in part, to protective immunity. Pansarbecovirus antibodies are desirable for broad protection, but the NTD region of SARS-CoV and SARS-CoV-2 exhibit a
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HMGA1 is a crucial mediator of colon tumorigenesis driven by the loss of APC J. Clin. Invest. (IF 13.3) Pub Date : 2025 Yuxiang Wang, Mikayla Ybarra, Zhenghe Wang
Colorectal cancer is the second leading cause of cancer death in the United States. The adenomatous polyposis coli (APC) pathway plays a critical role in colorectal tumorigenesis, but the mechanism is not fully understood. In this issue of the JCI, Luo and colleagues used genetically engineered mouse models to show that high mobility group A (HMGA1) is a critical mediator in the development of colon
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A deep intronic mutation causes RAD50 deficiency through an unusual mechanism of distant exon activation J. Clin. Invest. (IF 13.3) Pub Date : 2024 Kristine Bousset, Stefano Donega, Najim Ameziane, Tabea Fleischhammer, Dhanya Ramachandran, Miriam Poley-Gil, Detlev Schindler, Ingrid M. van de Laar, Franco Pagani, Thilo Dörk
To the editor: Human RAD50 deficiency is a very rare genomic instability syndrome associated with microcephaly and stunted growth (1). Here, we describe RAD50 deficiency in two siblings harboring a far-intronic RAD50 5 bp deletion (Δ5) in trans with a classic frameshift variant. The Δ5 mutation did not affect canonical splice sites but activated a poison 87 bp exon 30 nucleotides downstream. In the
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Vascular smooth muscle cell PRDM16 regulates circadian variation in blood pressure J. Clin. Invest. (IF 13.3) Pub Date : 2024 Zhenguo Wang, Wenjuan Mu, Juan Zhong, Ruiyan Xu, Yaozhong Liu, Guizhen Zhao, Yanhong Guo, Jifeng Zhang, Ida Surakka, Y. Eugene Chen, Lin Chang
Disruptions of blood pressure (BP) circadian variation are closely associated with an increased risk of cardiovascular disease. Thus, gaining insights into the molecular mechanisms of BP circadian variation is essential for comprehending BP regulation. Human genetic analyses suggest that PR domain–containing protein 16 (PRDM16), a transcription factor highly expressed in vascular smooth muscle cells
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HMGA1 acts as an epigenetic gatekeeper of ASCL2 and Wnt signaling during colon tumorigenesis J. Clin. Invest. (IF 13.3) Pub Date : 2025 Li Z. Luo, Jung-Hyun Kim, Iliana Herrera, Shaoguang Wu, Xinqun Wu, Seong-Sik Park, Juyoung Cho, Leslie Cope, Lingling Xian, Bailey E. West, Julian Calderon-Espinosa, Joseph Kim, Zanshé Thompson, Isha Maloo, Tatianna Larman, Karen L. Reddy, Ying Feng, Eric R. Fearon, Cynthia L. Sears, Linda Resar
Mutated tumor cells undergo changes in chromatin accessibility and gene expression, resulting in aberrant proliferation and differentiation, although how this occurs is unclear. HMGA1 chromatin regulators are abundant in stem cells and oncogenic in diverse tissues; however, their role in colon tumorigenesis is only beginning to emerge. Here, we uncover a previously unknown epigenetic program whereby
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Blood pressure regulation through circadian variation: PRDM16 as a target in vascular smooth muscle cells J. Clin. Invest. (IF 13.3) Pub Date : 2025 M. Adriana Cuibus, Omar Abdel-Wahab
The precise mechanisms of blood pressure (BP) regulation are not fully elucidated, and understanding BP regulation is crucial for managing hypertension and improving outcomes for cardiovascular disease. In this issue of the JCI, Wang et al. identified the transcription factor PR domain–containing protein 16 (PRDM16) as a regulator of both vascular smooth muscle cell contraction and the circadian response
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Lactobacillus rhamnosus GG induces STING-dependent IL-10 in intestinal monocytes and alleviates inflammatory colitis in mice J. Clin. Invest. (IF 13.3) Pub Date : 2025 Wei Si, Xin Zhao, Ruitong Li, Yaopeng Li, Cui Ma, Xiaohan Zhao, Jason Bugno, Yuchang Qin, Junmin Zhang, Hongwei Liu, Liangliang Wang
Preclinical and clinical observations indicate that the probiotic Lactobacillus rhamnosus GG (LGG) can modulate colonic inflammation. However, the underlying mechanisms have not been explored in depth. Here, we demonstrate that oral administration of live LGG alleviated inflammatory colitis by increasing IL-10 expression in intestinal Ly6C+ monocytes. Mechanistically, LGG induced IL-10 production via
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Ferumoxytol nanozymes effectively target chronic biofilm infections in apical periodontitis J. Clin. Invest. (IF 13.3) Pub Date : 2024 Alaa Babeer, Yuan Liu, Zhi Ren, Zhenting Xiang, Min Jun Oh, Nil Kanatha Pandey, Aurea Simon-Soro, Ranran Huang, Bekir Karabucak, David P. Cormode, Chider Chen, Hyun Koo
Bacterial biofilms are pervasive and recalcitrant to current antimicrobials, causing numerous infections. Iron oxide nanozymes, including an FDA-approved formulation, ferumoxytol (FMX), show potential against biofilm infections via catalytic activation of hydrogen peroxide (H2O2). However, clinical evidence regarding the efficacy and therapeutic mechanisms of FMX is lacking. Here, we investigate whether
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Cathelicidin antimicrobial peptide expression in neutrophils and neurons antagonistically modulates neuroinflammation J. Clin. Invest. (IF 13.3) Pub Date : 2024 Subash Chand Verma, Emmanuelle Enée, Kanchanadevi Manasse, Feriel Rebhi, Axelle Penc, David Romeo-Guitart, Cuc Bui Thi, Matthias Titeux, Franck Oury, Simon Fillatreau, Roland Liblau, Julien Diana
Multiple sclerosis (MS) is an autoimmune disease that affects the CNS, the pathophysiology of which remains unclear and for which there is no definitive cure. Antimicrobial peptides (AMPs) are immunomodulatory molecules expressed in various tissues, including the CNS. Here, we investigated whether the cathelicidin-related AMP (CRAMP) modulated the development of experimental autoimmune encephalomyelitis
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AAV9/SLC6A1 gene therapy rescues abnormal EEG patterns and cognitive behavioral deficiencies in Slc6a1–/– mice J. Clin. Invest. (IF 13.3) Pub Date : 2024 Weirui Guo, Matthew Rioux, Frances Shaffo, Yuhui Hu, Ze Yu, Chao Xing, Steven J. Gray
The solute carrier family 6 member 1 (SLC6A1) gene encodes the γ-aminobutyric acid (GABA) transporter GAT-1, the deficiency of which is associated with infantile encephalopathy with intellectual disability. We designed 2 AAV9 vectors, with either the JeT or MeP promoter, and conducted preclinical gene therapy studies using heterozygous and homozygous Slc6a1-KO mice at different developmental ages and
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Translational regulation of SND1 governs endothelial homeostasis during stress J. Clin. Invest. (IF 13.3) Pub Date : 2025 Zhenbo Han, Gege Yan, Jordan Jousma, Sarath Babu Nukala, Mehdi Amiri, Stephen Kiniry, Negar Tabatabaei, Youjeong Kwon, Sen Zhang, Jalees Rehman, Sandra Pinho, Sang-Bing Ong, Pavel V. Baranov, Soroush Tahmasebi, Sang-Ging Ong
Translational control shapes the proteome and is particularly important in regulating gene expression under stress. A key source of endothelial stress is treatment with tyrosine kinase inhibitors (TKIs), which lowers cancer mortality but increases cardiovascular mortality. Using a human induced pluripotent stem cell–derived endothelial cell (hiPSC-EC) model of sunitinib-induced vascular dysfunction
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ZDHHC18 promotes renal fibrosis development by regulating HRAS palmitoylation. J. Clin. Invest. (IF 13.3) Pub Date : 2025-02-04 Di Lu,Gulibositan Aji,Guanyu Li,Yue Li,Wenlin Fang,Shuai Zhang,Ruiqi Yu,Sheng Jiang,Xia Gao,Yuhang Jiang,Qi Wang
Fibrosis is the final common pathway leading to end stage chronic kidney disease (CKD). However, the function of protein palmitoylation in renal fibrosis and underlying mechanisms remain unclear. In this study, we observed that the expression of the palmitoyltransferase ZDHHC18 was significantly elevated in unilateral ureteral obstruction (UUO) and folic acid (FA)-induced renal fibrosis mouse models
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RNase L represses hair follicle regeneration through altered innate immune signaling. J. Clin. Invest. (IF 13.3) Pub Date : 2025-02-04 Charles S Kirby,Nasif Islam,Eric Wier,Martin P Alphonse,Evan Sweren,Gaofeng Wang,Haiyun Liu,Dongwon Kim,Ang Li,Sam S Lee,Andrew M Overmiller,Yingchao Xue,Sashank Reddy,Nathan K Archer,Lloyd S Miller,Jianshi Yu,Weiliang Huang,Jace W Jones,Sooah Kim,Maureen A Kane,Robert H Silverman,Luis A Garza
Mammalian injury responses are predominantly characterized by fibrosis and scarring rather than functional regeneration. This limited regenerative capacity in mammals could reflect a loss of pro-regeneration programs or active suppression by genes functioning akin to tumor suppressors. To uncover programs governing regeneration in mammals, we screened transcripts in human subjects following laser rejuvenation
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5-HT orchestrates Histone Serotonylation and Citrullination to Drive Neutrophil Extracellular Traps and Liver Metastasis. J. Clin. Invest. (IF 13.3) Pub Date : 2025-02-04 Kaiyuan Liu,Yingchao Zhang,Genyu Du,Xinyu Chen,Lingling Xiao,Luyao Jiang,Na Jing,Penghui Xu,Chaoxian Zhao,Yiyun Liu,Huifang Zhao,Yujiao Sun,Jinming Wang,Chaping Cheng,Deng Wang,Jiahua Pan,Wei Xue,Pengcheng Zhang,Zhi-Gang Zhang,Wei-Qiang Gao,Shu-Heng Jiang,Kai Zhang,Helen He Zhu
Serotonin (5-HT) is a neurotransmitter that has been linked to tumorigenesis. Whether and how 5-HT modulates cells in the microenvironment to regulate tumor metastasis remains to be largely unknown. Here, we demonstrate that 5-HT is secreted by neuroendocrine prostate cancer (NEPC) cells to communicate with neutrophils and to induce neutrophil extracellular traps (NETs) in the liver, which in turn
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Sleep-wake variation in body temperature regulates tau secretion and correlates with CSF and plasma tau. J. Clin. Invest. (IF 13.3) Pub Date : 2025-02-04 Geoffrey Canet,Felipe Da Gama Monteiro,Emma Rocaboy,Sofia Diego-Diaz,Boutheyna Khelaifia,Kelly Godbout,Aymane Lachhab,Jessica Kim,Daphne I Valencia,Audrey Yin,Hau-Tieng Wu,Jordan C Howell,Emily Blank,Francis Laliberté,Nadia Fortin,Emmanuelle Boscher,Parissa Fereydouni-Forouzandeh,Stéphanie Champagne,Isabelle Guisle,Sébastien S Hébert,Vincent Pernet,Haiyan Liu,William Lu,Ludovic Debure,David M Rapoport
Sleep disturbance is bidirectionally associated with increased risks of Alzheimer's disease and other tauopathies. While the sleep-wake cycle regulates interstitial and cerebrospinal fluid (CSF) tau levels, the underlying mechanisms remain unknown. Understanding these mechanisms is crucial given evidence indicates that tau pathology spreads through neuron-to-neuron transfer, involving the secretion
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Estrogen receptor alpha ablation reverses muscle fibrosis and inguinal hernias. J. Clin. Invest. (IF 13.3) Pub Date : 2025-02-04 Tanvi Potluri,Tianming You,Ping Yin,John S Coon V,Jonah J Stulberg,Yang Dai,David J Escobar,Richard L Lieber,Hong Zhao,Serdar E Bulun
Fibrosis of the lower abdominal muscle (LAM) contributes to muscle weakening and inguinal hernia formation, an ailment affecting a noteworthy fifty percent of men by age 75, necessitating surgical correction as the singular therapy. Despite its prevalence, the mechanisms driving LAM fibrosis and hernia development remain poorly understood. Utilizing a humanized mouse model that replicates elevated
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Glomerular Filtration Rate (GFR) Estimation with Cystatin C—Past, Present, and Future Clin. Chem. (IF 7.1) Pub Date : 2025-02-04 Amy B Karger, Michael G Shlipak
Background Cystatin C is a long-established filtration marker which can be used to assess kidney function, but it has been sparingly used for clinical care due to creatinine’s role as the primary biomarker for kidney function assessment based on estimated glomerular filtration rate (eGFR). Content This review summarizes the evolution of cystatin C’s role in kidney disease assessment and highlights
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An Unexpectedly High IgE Level during Allergic Exploration. Clin. Chem. (IF 7.1) Pub Date : 2025-02-03 Guillaume Feugray,Jennifer Guillerme,Stéphanie Pramil,Marion Carrette,Muriel Quillard Muraine
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Commentary on Hiding in Plain Sight: Protein Electrophoresis Profile Inconsistent with Patient's Diagnosis. Clin. Chem. (IF 7.1) Pub Date : 2025-02-03 Jing Cao
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New American Society of Hematology Thrombophilia Guidelines Could Provoke Surge in Laboratory Testing. Clin. Chem. (IF 7.1) Pub Date : 2025-02-03 Anna E Merrill,Steven R Lentz
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Commentary on Hiding in Plain Sight: Protein Electrophoresis Profile Inconsistent with Patient's Diagnosis. Clin. Chem. (IF 7.1) Pub Date : 2025-02-03 Melissa R Snyder
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Hiding in Plain Sight: Protein Electrophoresis Profile Inconsistent with Patient's Diagnosis. Clin. Chem. (IF 7.1) Pub Date : 2025-02-03 Vrajesh Pandya,Julio C Delgado
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Commentary on An Unexpectedly High IgE Level during Allergic Exploration. Clin. Chem. (IF 7.1) Pub Date : 2025-02-03 Rebecca S Treger
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Persistent Unexplained Polyclonal IgA Gammopathy in a Patient with Multiple Myeloma. Clin. Chem. (IF 7.1) Pub Date : 2025-02-03 Paul E Young,Heba Badr,Anthony O Okorodudu
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Commentary on An Unexpectedly High IgE Level during Allergic Exploration. Clin. Chem. (IF 7.1) Pub Date : 2025-02-03 Louis Nevejan,Xavier Bossuyt
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Transcription of hepatitis B surface antigen shifts from cccDNA to integrated HBV DNA during treatment. J. Clin. Invest. (IF 13.3) Pub Date : 2025-01-30 Maraake Taddese,Tanner Grudda,Giulia Belluccini,Mark Anderson,Gavin Cloherty,Hyon S Hwang,Monika Mani,Che-Min Lo,Naomi Esrig,Mark S Sulkowski,Richard K Sterling,Yang Zhang,Ruy M Ribeiro,David L Thomas,Chloe L Thio,Ashwin Balagopal
The cornerstone of functional cure for chronic hepatitis B (CHB) is hepatitis B surface antigen (HBsAg) loss from blood. HBsAg is encoded by covalently closed circular DNA (cccDNA) and HBV DNA integrated into the host genome (iDNA). Nucleos(t)ide analogues (NUCs), the mainstay of CHB treatment, rarely lead to HBsAg loss, which we hypothesized was due to continued iDNA transcription despite decreased
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HoxBlinc lncRNA reprograms CTCF-independent TADs to drive leukemic transcription and HSC dysregulation in NUP98-rearranged leukemia. J. Clin. Invest. (IF 13.3) Pub Date : 2025-01-30 Karina Hamamoto,Ganqian Zhu,Qian Lai,Julia Lesperance,Huacheng Luo,Ying Li,Nupur Nigam,Arati Sharma,Feng-Chun Yang,David Claxton,Yi Qiu,Peter D Aplan,Mingjiang Xu,Suming Huang
Although nucleoporin 98 (NUP98) fusion oncogenes often drive aggressive pediatric leukemia by altering chromatin structure and expression of HOX genes, underlying mechanisms remain elusive. Here, we report that a Hoxb-associated lncRNA HoxBlinc was aberrantly activated in NUP98-PHF23 fusion-driven leukemias. HoxBlinc chromatin occupancies led to elevated MLL1 recruitment and aberrant homeotic topologically
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Monocytes and interstitial macrophages contribute to hypoxic pulmonary hypertension. J. Clin. Invest. (IF 13.3) Pub Date : 2025-01-30 Rahul Kumar,Kevin Nolan,Biruk Kassa,Neha Chanana,Tsering Palmo,Kavita Sharma,Kanika Singh,Claudia Mickael,Dara Fonseca Balladares,Julia Nilsson,Amit Prabhakar,Aastha Mishra,Michael H Lee,Linda Sanders,Sushil Kumar,Ari B Molofsky,Kurt R Stenmark,Dean Sheppard,Rubin M Tuder,Mohit D Gupta,Tashi Thinlas,Qadar Pasha,Brian B Graham
Hypoxia is a major cause of pulmonary hypertension (PH) worldwide, and it is likely that interstitial pulmonary macrophages contribute to this vascular pathology. We observed in hypoxia-exposed mice an increase in resident interstitial macrophages, which expanded through proliferation and expressed the monocyte recruitment ligand CCL2. We also observed an increase in CCR2+ macrophages through recruitment
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Elevated protein lactylation promotes immunosuppressive microenvironment and therapeutic resistance in pancreatic ductal adenocarcinoma. J. Clin. Invest. (IF 13.3) Pub Date : 2025-01-30 Kang Sun,Xiaozhen Zhang,Jiatao Shi,Jinyan Huang,Sicheng Wang,Xiang Li,Haixiang Lin,Danyang Zhao,Mao Ye,Sirui Zhang,Li Qiu,Minqi Yang,Chuyang Liao,Lihong He,Mengyi Lao,Jinyuan Song,Na Lu,Yongtao Ji,Hanshen Yang,Lingyue Liu,Xinyuan Liu,Yan Chen,Shicheng Yao,Qianhe Xu,Jieru Lin,Yan Mao,Jingxin Zhou,Xiao Zhi,Ke Sun,Xiongbin Lu,Xueli Bai,Tingbo Liang
Metabolic reprogramming shapes tumor microenvironment (TME) and may lead to immunotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Elucidating the impact of pancreatic cancer cell metabolism in the TME is essential to therapeutic interventions. "Immune cold" PDAC is characterized by elevated lactate levels resulting from tumor cell metabolism, abundance of pro-tumor macrophages, and reduced
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Small Remnants versus Large Triglyceride-Rich Lipoproteins in Risk of Atherosclerotic Cardiovascular Disease. Clin. Chem. (IF 7.1) Pub Date : 2025-01-30 Benjamin N Wadström,Anders B Wulff,Kasper M Pedersen,Børge G Nordestgaard
BACKGROUND Small remnants may penetrate the arterial intima more efficiently compared to large triglyceride-rich lipoproteins (TGRL). We tested the hypothesis that the importance of remnant cholesterol for the risk of atherosclerotic cardiovascular disease (ASCVD) may depend on the size of the remnants and TGRL carrying cholesterol. METHODS The cholesterol content of small remnants and large TGRL were
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The Role of Laboratory Medicine in Improving Maternal Health Outcomes and Reducing Disparities. Clin. Chem. (IF 7.1) Pub Date : 2025-01-29 Vahid Azimi,Ann M Gronowski
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Small molecule modulators of B56-PP2A restore 4E-BP function to suppress eIF4E-dependent translation in cancer cells. J. Clin. Invest. (IF 13.3) Pub Date : 2025-01-27 Michelle A Lum,Kayla A Jonas,Shreya Parmar,Adrian R Black,Caitlin M O'Connor,Stephanie Dobersch,Naomi Yamamoto,Tess M Robertson,Aidan Schutter,Miranda Giambi,Rita A Avelar,Analisa DiFeo,Nicholas T Woods,Sita Kugel,Goutham Narla,Jennifer D Black
Dysregulated eIF4E-dependent translation is a central driver of tumorigenesis and therapy resistance. eIF4E binding proteins (4E-BP1/2/3) are major negative regulators of eIF4E-dependent translation that are inactivated in tumors through inhibitory phosphorylation or downregulation. Previous studies have linked PP2A phosphatase(s) to activation of 4E-BP1. Here, we leveraged biased small molecule activators
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Reflecting on 70 Years of Clinical Chemistry. Clin. Chem. (IF 7.1) Pub Date : 2025-02-03 Jason Y Park
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Neonatal but not Juvenile Gene Therapy Reduces Seizures and Prolongs Lifespan in SCN1B-Dravet Syndrome Mice. J. Clin. Invest. (IF 13.3) Pub Date : 2025-01-23 Chunling Chen,Yukun Yuan,Heather A O'Malley,Robert Duba-Kiss,Yan Chen,Karl Habig,Yosuke Niibori,Samantha L Hodges,David R Hampson,Lori L Isom
Dravet syndrome (DS) is a developmental and epileptic encephalopathy (DEE) that begins in the first year of life. While most cases of DS are caused by variants in SCN1A, variants in SCN1B, encoding voltage-gated sodium channel β1 subunits, are also linked to DS or to the more severe early infantile DEE. Both disorders fall under the OMIM term DEE52. Scn1b null mice model DEE52, with spontaneous generalized
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Human Oncostatin M deficiency underlies an inherited severe bone marrow failure syndrome. J. Clin. Invest. (IF 13.3) Pub Date : 2025-01-23 Alexandrine Garrigue,Laëtitia Kermasson,Sandrine Susini,Ingrid Fert,Christopher B Mahony,Hanem Sadek,Sonia Luce,Myriam Chouteau,Marina Cavazzana,Emmanuelle Six,Marie-Caroline Le Bousse-Kerdilès,Adrienne Anginot,Jean-Baptiste Souraud,Valérie Cormier-Daire,Marjolaine Willems,Anne Sirvent,Jennifer Russello,Isabelle Callebaut,Isabelle André,Julien Y Bertrand,Chantal Lagresle-Peyrou,Patrick Revy
Oncostatin M (OSM) is a cytokine with the unique ability to interact with both the OSM receptor (OSMR) and the leukemia inhibitory factor receptor (LIFR). On the other hand, OSMR interacts with IL31RA to form the interleukin-31 receptor. This intricate network of cytokines and receptors makes it difficult to understand the specific function of OSM. While monoallelic loss-of-function (LoF) mutations
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A whole-body imaging technique for tumor-specific diagnostics and screening of B7-H3-targeted therapies. J. Clin. Invest. (IF 13.3) Pub Date : 2025-01-23 Lei Xia,Yan Wu,Yanan Ren,Zhen Wang,Nina Zhou,Wenyuan Zhou,Lixin Zhou,Ling Jia,Chengxue He,Xiangxi Meng,Hua Zhu,Zhi Yang
BACKGROUND B7-H3 or CD276 is notably overexpressed in various malignant tumor cells in humans, with extremely high expression rates. The development of a radiotracer that targets B7-H3 may provide a universal tumor-specific imaging agent and allow the noninvasive assessment of the whole-body distribution of B7-H3-expressing lesions. METHODS We enhanced and optimized the structure of an affibody (ABY)
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Targeting allograft inflammatory factor-1 reprograms kidney macrophages to enhance repair. J. Clin. Invest. (IF 13.3) Pub Date : 2025-01-21 Irma Husain,Holly Shah,Collin Z Jordan,Naveen R Natesh,Olivia K Fay,Yanting Chen,Jamie R Privratsky,Hiroki Kitai,Tomokazu Souma,Shyni Varghese,David N Howell,Edward B Thorp,Xunrong Luo
The role of macrophages remains incompletely understood in kidney injury and repair. Their plasticity offers an opportunity to polarize them towards mediating injury resolution in both native and transplanted kidneys undergoing ischemia and/or rejection. Here, we show that infiltrating kidney macrophages augmented their AIF-1 expression after injury. Aif1 genetic deletion led to macrophage polarization
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Sex dimorphism in the mouse bone marrow niche regulates hematopoietic engraftment via sex-specific Kdm5c/Cxcl12 signaling. J. Clin. Invest. (IF 13.3) Pub Date : 2025-01-21 Xiaojing Cui,Liming Hou,Bowen Yan,Jinpeng Liu,Cuiping Zhang,Pinpin Sui,Sheng Tong,Larry Luchsinger,Avital Mendelson,Daohong Zhou,Feng-Chun Yang,Hui Zhong,Ying Liang
The bone marrow (BM) niche is critical in regulating hematopoiesis, and sexual dimorphism and its underlying mechanism in BM niche and its impact on hematopoiesis are not well understood. We show that male mice exhibited a higher abundance of leptin-receptor-expressing mesenchymal stromal cells (LepR-MSCs) compared to female mice. Sex-mismatched co-culture and BM transplantation showed that the male